Sustained CaMKII delta isoform gene expression is required for long lasting memories

ZALCMAN, GISELA; FEDERMAN, NOEL; FISZBEIN, ANA; DE LA FUENTE, VERÓNICA; AMENEIRO, LEILA; SCHOR, IGNACIO; ROMANO, ARTURO

MOLECULAR NEUROBIOLOGY

HUMANA PRESS INC

Lugar: Oregon; Año: 2018

0893-7648

Although important information is available on the molecular mechanisms of long-term memory formation, little is known about the processes underlying memory persistence and maintenance in the brain. Here, we report that persistent gene expression of CaMKII isoform participate in novel object recognition (NOR) memory in mice hippocampus. Antisense DNA infusion in hippocampus during NOR consolidation impairs 7 days but not 1 day memory, supporting a role of CaMKII in memory persistence. Its prolonged gene expression paralleled memory retention, being present at least for 7 days and decaying 20 days after training. Antisense infusion in hippocampus once memory is already consolidated impairs 7 days memory, supporting a role of CaMKII delta in memory maintenance. CaMKIIgene expression was accompanied by long-lasting nucleosome occupancy changes at its promoter. This epigenetic mechanism is described for the first time in a memory process and offers a novel mechanism for persistent gene expression. CaMKII delta protein is mainly present in nucleus and presynaptic terminals, suggesting a role in these subcellular compartments. All these results point to a key function of the sustained gene expression of this overlooking CaMKII isoform in long lasting memories.